Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the catalytic domains of serine/threonine-specific and tyrosine-specific protein kinases. It also includes RIO kinases, which are atypical serine protein kinases, aminoglycoside phosphotransferases, and choline kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to hydroxyl groups in specific substrates such as serine, threonine, or tyrosine residues of proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2318795510 156 YHNRQRLDMEDpSCEMCLSKDKTLQDLVYDLSTSgsgSGKPGIAHRDLKSKNILVKKNGMCAIADLGLAVRHDAVTDTID 235
Cdd:cd14143    83 YLNRYTVTVEG-MIKLALSIASGLAHLHMEIVGT---QGKPAIAHRDLKSKNILVKKNGTCCIADLGLAVRHDSATDTID 158

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2318795510 236 IAPNQRVGTKRYMAPEVLDETINMKHFDSFKCADIYALGLVYWEIARRCNSGGVHEEYQLPYYDLVPSDPSIEEMRKVVC 315
Cdd:cd14143   159 IAPNHRVGTKRYMAPEVLDDTINMKHFESFKRADIYALGLVFWEIARRCSIGGIHEDYQLPYYDLVPSDPSIEEMRKVVC 238

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 2318795510 316 DQKLRPNIPNWWQSYEALRVMGKMMRECWYANGAARLTALRIKKTLSQLS 365
Cdd:cd14143   239 EQKLRPNIPNRWQSCEALRVMAKIMRECWYANGAARLTALRIKKTLSQLS 288

Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta Type I Receptor and Activin Type IB/IC Receptors; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TGFbR1, also called Activin receptor-Like Kinase 5 (ALK5), functions as a receptor for TGFbeta and phoshorylates SMAD2/3. TGFbeta proteins are cytokines that regulate cell growth, differentiation, and survival, and are critical in the development and progression of many human cancers. Mutations in TGFbR1 (and TGFbR2) can cause aortic aneurysm disorders such as Loeys-Dietz and Marfan syndromes. ACVR1b (also called ALK4) and ACVR1c (also called ALK7) act as receptors for activin A and B, respectively. TGFbR1, ACVR1b, and ACVR1c belong to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like TGFbR1, ACVR1b, and ACVR1c, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The TGFbR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2318795510 156 YHNRQRLDMEDpSCEMCLSKDKTLQDLVYDLSTSgsgSGKPGIAHRDLKSKNILVKKNGMCAIADLGLAVRHDAVTDTID 235
Cdd:cd14143    83 YLNRYTVTVEG-MIKLALSIASGLAHLHMEIVGT---QGKPAIAHRDLKSKNILVKKNGTCCIADLGLAVRHDSATDTID 158

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2318795510 236 IAPNQRVGTKRYMAPEVLDETINMKHFDSFKCADIYALGLVYWEIARRCNSGGVHEEYQLPYYDLVPSDPSIEEMRKVVC 315
Cdd:cd14143   159 IAPNHRVGTKRYMAPEVLDDTINMKHFESFKRADIYALGLVFWEIARRCSIGGIHEDYQLPYYDLVPSDPSIEEMRKVVC 238

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 2318795510 316 DQKLRPNIPNWWQSYEALRVMGKMMRECWYANGAARLTALRIKKTLSQLS 365
Cdd:cd14143   239 EQKLRPNIPNRWQSCEALRVMAKIMRECWYANGAARLTALRIKKTLSQLS 288

Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or threonine-specific kinase subfamily.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2318795510  197 GIAHRDLKSKNILVKKNGMCAIADLGLA--VRHDAVTDTIdiapnqrVGTKRYMAPEVLDETinmKHfdSFKCaDIYALG 274
Cdd:smart00220 117 GIVHRDLKPENILLDEDGHVKLADFGLArqLDPGEKLTTF-------VGTPEYMAPEVLLGK---GY--GKAV-DIWSLG 183

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2318795510  275 LVYWEIARRcnsggvheeyQLPYYDlvpsDPSIEEMRKVVCDQKLRPNIPNWWQSYEALRVMGKMMRecwyANGAARLTA 354
Cdd:smart00220 184 VILYELLTG----------KPPFPG----DDQLLELFKKIGKPKPPFPPPEWDISPEAKDLIRKLLV----KDPEKRLTA 245

                   ....*
gi 2318795510  355 LRIKK 359
Cdd:smart00220 246 EEALQ 250

Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyze the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyze the reverse process. Protein kinases fall into three broad classes, characterized with respect to substrate specificity; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2318795510 200 HRDLKSKNILVKKNGMCAIADLGLAvrhdavtDTIDIAPNQRVGTK-----RYMAPEVLDEtinmKHFdSFKcADIYALG 274
Cdd:pfam07714 125 HRDLAARNCLVSENLVVKISDFGLS-------RDIYDDDYYRKRGGgklpiKWMAPESLKD----GKF-TSK-SDVWSFG 191

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2318795510 275 LVYWEIArrcnSGGvheeyQLPYYDLVPsdpsiEEMRKVVCDQKlRPNIP-NWWQS-YEalrvmgkMMRECWYANGAARL 352
Cdd:pfam07714 192 VLLWEIF----TLG-----EQPYPGMSN-----EEVLEFLEDGY-RLPQPeNCPDElYD-------LMKQCWAYDPEDRP 249

                  ....*....
gi 2318795510 353 TALRIKKTL 361
Cdd:pfam07714 250 TFSELVEDL 258

serine/threonine-protein kinase PknD;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2318795510 197 GIAHRDLKSKNILVKKNGMCAIADLGLAVRHDAVTDT-IDIAPNQR-------------VGTKRYMAPEVLdetinmKHF 262
Cdd:PRK13184  133 GVLHRDLKPDNILLGLFGEVVILDWGAAIFKKLEEEDlLDIDVDERnicyssmtipgkiVGTPDYMAPERL------LGV 206

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2318795510 263 DSFKCADIYALGLVYWEIA------RRCNSGGVHEEYQL-------PYYDLVPSDPSIeEMRKVVCDQKLRpnipnwWQS 329
Cdd:PRK13184  207 PASESTDIYALGVILYQMLtlsfpyRRKKGRKISYRDVIlspievaPYREIPPFLSQI-AMKALAVDPAER------YSS 279

                  ....*
gi 2318795510 330 YEALR 334
Cdd:PRK13184  280 VQELK 284

Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta Type I Receptor and Activin Type IB/IC Receptors; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TGFbR1, also called Activin receptor-Like Kinase 5 (ALK5), functions as a receptor for TGFbeta and phoshorylates SMAD2/3. TGFbeta proteins are cytokines that regulate cell growth, differentiation, and survival, and are critical in the development and progression of many human cancers. Mutations in TGFbR1 (and TGFbR2) can cause aortic aneurysm disorders such as Loeys-Dietz and Marfan syndromes. ACVR1b (also called ALK4) and ACVR1c (also called ALK7) act as receptors for activin A and B, respectively. TGFbR1, ACVR1b, and ACVR1c belong to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like TGFbR1, ACVR1b, and ACVR1c, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The TGFbR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2318795510 156 YHNRQRLDMEDpSCEMCLSKDKTLQDLVYDLSTSgsgSGKPGIAHRDLKSKNILVKKNGMCAIADLGLAVRHDAVTDTID 235
Cdd:cd14143    83 YLNRYTVTVEG-MIKLALSIASGLAHLHMEIVGT---QGKPAIAHRDLKSKNILVKKNGTCCIADLGLAVRHDSATDTID 158

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2318795510 236 IAPNQRVGTKRYMAPEVLDETINMKHFDSFKCADIYALGLVYWEIARRCNSGGVHEEYQLPYYDLVPSDPSIEEMRKVVC 315
Cdd:cd14143   159 IAPNHRVGTKRYMAPEVLDDTINMKHFESFKRADIYALGLVFWEIARRCSIGGIHEDYQLPYYDLVPSDPSIEEMRKVVC 238

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 2318795510 316 DQKLRPNIPNWWQSYEALRVMGKMMRECWYANGAARLTALRIKKTLSQLS 365
Cdd:cd14143   239 EQKLRPNIPNRWQSCEALRVMAKIMRECWYANGAARLTALRIKKTLSQLS 288

Catalytic domain of Transforming Growth Factor beta Receptor-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of receptors for the TGFbeta family of secreted signaling molecules including TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. There are two types of TGFbeta receptors included in this subfamily, I and II, that play different roles in signaling. For signaling to occur, the ligand first binds to the high-affinity type II receptor, which is followed by the recruitment of the low-affinity type I receptor to the complex and its activation through trans-phosphorylation by the type II receptor. The active type I receptor kinase starts intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. Different ligands interact with various combinations of types I and II receptors to elicit a specific signaling pathway. Activins primarily signal through combinations of ACVR1b/ALK7 and ACVR2a/b; myostatin and GDF11 through TGFbR1/ALK4 and ACVR2a/b; BMPs through ACVR1/ALK1 and BMPR2; and TGFbeta through TGFbR1 and TGFbR2. The TGFbR-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2318795510 156 YHNRQRLDMEDpSCEMCLSKDKTLQDLVYDLStsGSGSGKPGIAHRDLKSKNILVKKNGMCAIADLGLAVRHDAVTDTID 235
Cdd:cd13998    83 YLSLHTIDWVS-LCRLALSVARGLAHLHSEIP--GCTQGKPAIAHRDLKSKNILVKNDGTCCIADFGLAVRLSPSTGEED 159

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2318795510 236 IAPNQRVGTKRYMAPEVLDETINMKHFDSFKCADIYALGLVYWEIARRCNS-GGVHEEYQLPYYDLVPSDPSIEEMRKVV 314
Cdd:cd13998   160 NANNGQVGTKRYMAPEVLEGAINLRDFESFKRVDIYAMGLVLWEMASRCTDlFGIVEEYKPPFYSEVPNHPSFEDMQEVV 239

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 2318795510 315 CDQKLRPNIPNWWQSYEALRVMGKMMRECWYANGAARLTALRIKKTLSQL 364
Cdd:cd13998   240 VRDKQRPNIPNRWLSHPGLQSLAETIEECWDHDAEARLTAQCIEERLSEF 289

Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type I Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR1 functions as a receptor for morphogenetic proteins (BMPs), which are involved in the regulation of cell proliferation, survival, differentiation, and apoptosis. BMPs are able to induce bone, cartilage, ligament, and tendon formation, and may play roles in bone diseases and tumors. Vertebrates contain two type I BMP receptors, BMPR1a and BMPR1b. BMPR1 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that also includes TGFbeta, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like BMPR1, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The BMPR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2318795510 194 GKPGIAHRDLKSKNILVKKNGMCAIADLGLAVRHDAVTDTIDIAPNQRVGTKRYMAPEVLDETINMKHFDSFKCADIYAL 273
Cdd:cd14144   117 GKPAIAHRDIKSKNILVKKNGTCCIADLGLAVKFISETNEVDLPPNTRVGTKRYMAPEVLDESLNRNHFDAYKMADMYSF 196

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2318795510 274 GLVYWEIARRCNSGGVHEEYQLPYYDLVPSDPSIEEMRKVVCDQKLRPNIPNWWQSYEALRVMGKMMRECWYANGAARLT 353
Cdd:cd14144   197 GLVLWEIARRCISGGIVEEYQLPYYDAVPSDPSYEDMRRVVCVERRRPSIPNRWSSDEVLRTMSKLMSECWAHNPAARLT 276

                         170
                  ....*....|.
gi 2318795510 354 ALRIKKTLSQL 364
Cdd:cd14144   277 ALRVKKTLGKL 287

Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IA Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR1a, also called Activin receptor-Like Kinase 3 (ALK3), functions as a receptor for bone morphogenetic proteins (BMPs), which are involved in the regulation of cell proliferation, survival, differentiation, and apoptosis. BMPs are able to induce bone, cartilage, ligament, and tendon formation, and may play roles in bone diseases and tumors. Germline mutations in BMPR1a are associated with an increased risk to Juvenile Polyposis Syndrome, a hamartomatous disorder that may lead to gastrointestinal cancer. BMPR1a may also play an indirect role in the development of hematopoietic stem cells (HSCs) as osteoblasts are a major component of the HSC niche within the bone marrow. BMPR1a belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like BMPR1a, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The BMPR1a subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2318795510 194 GKPGIAHRDLKSKNILVKKNGMCAIADLGLAVRHDAVTDTIDIAPNQRVGTKRYMAPEVLDETINMKHFDSFKCADIYAL 273
Cdd:cd14220   117 GKPAIAHRDLKSKNILIKKNGTCCIADLGLAVKFNSDTNEVDVPLNTRVGTKRYMAPEVLDESLNKNHFQAYIMADIYSF 196

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2318795510 274 GLVYWEIARRCNSGGVHEEYQLPYYDLVPSDPSIEEMRKVVCDQKLRPNIPNWWQSYEALRVMGKMMRECWYANGAARLT 353
Cdd:cd14220   197 GLIIWEMARRCVTGGIVEEYQLPYYDMVPSDPSYEDMREVVCVKRLRPTVSNRWNSDECLRAVLKLMSECWAHNPASRLT 276

                         170
                  ....*....|.
gi 2318795510 354 ALRIKKTLSQL 364
Cdd:cd14220   277 ALRIKKTLAKM 287

Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Type II Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TGFbR2 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. Type II receptors, such as TGFbR2, are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. TGFbR2 acts as the receptor for TGFbeta, which is crucial in growth control and homeostasis in many different tissues. It plays roles in regulating apoptosis and in maintaining the balance between self renewal and cell loss. It also plays a key role in maintaining vascular integrity and in regulating responses to genotoxic stress. Mutations in TGFbR2 can cause aortic aneurysm disorders such as Loeys-Dietz and Marfan syndromes. The TGFbR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2318795510 151 YHQ----RVYHNRQRLDMEDpSCEMCLSKDKTLQDLVYDlsTSGSGSGKPGIAHRDLKSKNILVKKNGMCAIADLGLAVR 226
Cdd:cd14055    80 YHEngslQDYLTRHILSWED-LCKMAGSLARGLAHLHSD--RTPCGRPKIPIAHRDLKSSNILVKNDGTCVLADFGLALR 156

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2318795510 227 HDAVTDTIDIAPNQRVGTKRYMAPEVLDETINMKHFDSFKCADIYALGLVYWEIARRCNSGGVHEEYQLPYYDLVPSDPS 306
Cdd:cd14055   157 LDPSLSVDELANSGQVGTARYMAPEALESRVNLEDLESFKQIDVYSMALVLWEMASRCEASGEVKPYELPFGSKVRERPC 236

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*...
gi 2318795510 307 IEEMRKVVCDQKLRPNIPNWWQSYEALRVMGKMMRECWYANGAARLTA 354
Cdd:cd14055   237 VESMKDLVLRDRGRPEIPDSWLTHQGMCVLCDTITECWDHDPEARLTA 284

Catalytic domain of the Serine/Threonine Kinase, Activin Type IIA Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR2a (or ActRIIA) belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. ACVR2b is one of two ACVR2 receptors found in vertebrates. Type II receptors are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. ACVR2 acts primarily as the receptors for activins, nodal, myostatin, GDF11, and a subset of BMPs. ACVR2 signaling impacts many cellular and physiological processes including reproductive and gonadal functions, myogenesis, bone remodeling and tooth development, kidney organogenesis, apoptosis, fibrosis, inflammation, and neurogenesis. The ACVR2a subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2318795510 170 EMCLSKDKTLQDLVY---DLSTSGSGSgKPGIAHRDLKSKNILVKKNGMCAIADLGLAVRHDAVTDTIDIapNQRVGTKR 246
Cdd:cd14141    93 ELCHIAQTMARGLAYlheDIPGLKDGH-KPAIAHRDIKSKNVLLKNNLTACIADFGLALKFEAGKSAGDT--HGQVGTRR 169

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2318795510 247 YMAPEVLDETINMKHfDSFKCADIYALGLVYWEIARRCN-SGGVHEEYQLPYYDLVPSDPSIEEMRKVVCDQKLRPNIPN 325
Cdd:cd14141   170 YMAPEVLEGAINFQR-DAFLRIDMYAMGLVLWELASRCTaSDGPVDEYMLPFEEEVGQHPSLEDMQEVVVHKKKRPVLRE 248

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 2318795510 326 WWQSYEALRVMGKMMRECWYANGAARLTALRIKKTLSQLSVQ 367
Cdd:cd14141   249 CWQKHAGMAMLCETIEECWDHDAEARLSAGCVEERIIQMQRL 290

extracellular domain (ECD) found in activin receptor-like kinase 4 (ALK-4) and similar proteins; ALK-4 (EC 2.7.11.30, also called ACVRLK4, or activin receptor type-1B (ACVR1B), or activin receptor type IB (ACTR-IB), or serine/threonine-protein kinase receptor R2 (SKR2)) is the transmembrane serine/threonine kinase activin type-1 receptor forming an activin receptor complex with activin receptor type-2 (ACVR2A or ACVR2B). It transduces the activin signal from the cell surface to the cytoplasm and is thus regulating many physiological and pathological processes including neuronal differentiation and neuronal survival, hair follicle development and cycling, FSH production by the pituitary gland, wound healing, extracellular matrix production, immunosuppression, and carcinogenesis. This model corresponds to the extracellular domain (ECD) of ALK-4, which belongs to Ly-6 antigen/uPA receptor-like (LU) superfamily and exhibits a snake toxin-like fold (also known as three-finger toxin/3FTx fold or three-fingered protein/TFP domain fold).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2318795510  30 QALLCACTSCLQaNYTCETDGACMVSIFNL-DGMEHHVRTCIPKVELVPAGKPFYCLSSEDLR---NTHCCY-TDYCN 102
Cdd:cd23536     1 EGLKCVCSDCTN-NGTCETDGYCLVSITIDkDGEIKIRRTCIDKDKLFPPGRPFFCLSSEDLLhnsNVHCCNdEDFCN 77

extracellular domain (ECD) found in Drosophila melanogaster Baboon and similar proteins; Baboon (Babo) is the Drosophila transforming growth factor-beta (TGF-beta)/activin-specific type I receptor that transmits signals through dSmad2. Baboon/dSmad2-mediated TGF-beta signaling is required during late larval stage for development of adult-specific neurons. In addition to dSmad2, it can Mad and bone morphogenetic protein (BMP)-specific R-Smad. Baboon is the ortholog of the human activin receptor-like kinase (ALK)-4/5/7. It contains an extracellular domain (ECD), which belongs to Ly-6 antigen/uPA receptor-like (LU) superfamily and exhibits a snake toxin-like fold (also known as three-finger toxin/3FTx fold or three-fingered protein/TFP domain fold).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2318795510  32 LLCACTSCLQANYTCETDGACMVSIFNL-DGMEHHVRTCIPKVELVPAGKPFYCLSSEDLRNTH---CCY-TDYCNR 103
Cdd:cd23598     1 LKCYCDICKKTNYTCETDGVCFTSTSLVkNGVIEYSYRCLDKKRLFPPENPLICHSSKPRNDTFvikCCKdYDFCNR 77

extracellular domain (ECD) found in activin receptor-like kinase 5 (ALK-5) and similar proteins; ALK-5 (EC 2.7.11.30, also called TGF-beta receptor type-1 (TGFR-1), or activin A receptor type II-like protein kinase of 53kD, or serine/threonine-protein kinase receptor R4 (SKR4), or TGF-beta type I receptor, or transforming growth factor-beta receptor type I (TGFBR1), or TGF-beta receptor type I (TbetaR-I)) is the transmembrane serine/threonine kinase forming with the TGF-beta type II serine/threonine kinase receptor, TGFBR2, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2, and TGFB3. It transduces the TGFB1, TGFB2, and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression, and carcinogenesis. This model corresponds to the extracellular domain (ECD) of ALK-5, which belongs to Ly-6 antigen/uPA receptor-like (LU) superfamily and exhibits a snake toxin-like fold (also known as three-finger toxin/3FTx fold or three-fingered protein/TFP domain fold).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2318795510  32 LLCACTSCLQaNYTCETDGACMVSIFNLDGMEHHVRTCIPKVELVPAGKPFYCLSS---EDLRNTHCCYTDYCNR 103
Cdd:cd23537     1 LQCYCHLCTK-NFTCVTDGLCFVSVTRSTDKVIHNSMCIAEIDLIPRDRPFVCAPSskdGSSTHPYCCNTDHCNK 74

extracellular domain (ECD) found in activin receptor-like kinase 7 (ALK-7) and similar proteins; ALK-7 (EC 2.7.11.30, also called activin receptor type-1C (ACVR1C), or activin receptor type IC (ACTR-IC)) is a serine/threonine protein kinase which forms a receptor complex on ligand binding. The receptor complex consisting of 2 type II and 2 type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators, SMAD2 and SMAD3. ALK-7 is the receptor for activin AB, activin B, and NODAL. It plays a role in cell differentiation, growth arrest and apoptosis. This model corresponds to the extracellular domain (ECD) of ALK-7, which belongs to Ly-6 antigen/uPA receptor-like (LU) superfamily and exhibits a snake toxin-like fold (also known as three-finger toxin/3FTx fold or three-fingered protein/TFP domain fold).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2318795510  31 ALLCACTSCLQANYTCETDGACMVSIFNLDGMEHHVRTCIPKVELvpaGKPFYCLSSEDLRNTHCCYTDYCNRIDLRV 108
Cdd:cd23540     2 GLKCVCLLCEHTNYTCQTEGACWTSVMLTNGKEEVIKSCVSLPEL---NAQVFCHSSNNVTKTECCFTDFCNNITLHL 76

Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. This family is composed of STKs, and some dual-specificity PKs that phosphorylate both threonine and tyrosine residues of target proteins. Most members are kinases involved in mitogen-activated protein kinase (MAPK) signaling cascades, acting as MAPK kinases (MAPKKs), MAPKK kinases (MAPKKKs), or MAPKKK kinases (MAP4Ks). The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPKK, which itself is phosphorylated and activated by a MAPKKK. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAPKKK to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Other STE family members include p21-activated kinases (PAKs) and class III myosins, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain, which can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, as well as autophosphorylate the C-terminal motor domain. They play an important role in maintaining the structural integrity of photoreceptor cell microvilli. The STE family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2318795510 197 GIAHRDLKSKNILVKKNGMCAIADLGLAVRhdaVTDTIDiaPNQRVGTKRYMAPEVldetINMKHFDsFKCaDIYALGLV 276
Cdd:cd05122   118 GIIHRDIKAANILLTSDGEVKLIDFGLSAQ---LSDGKT--RNTFVGTPYWMAPEV----IQGKPYG-FKA-DIWSLGIT 186

                          90       100
                  ....*....|....*....|....*.
gi 2318795510 277 YWEIARRcnsggvheeyQLPYYDLVP 302
Cdd:cd05122   187 AIEMAEG----------KPPYSELPP 202

Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2318795510 197 GIAHRDLKSKNILVKKNGMCAIADLGLAVRHDAVTDTidiAPNQRVGTKRYMAPE-VLDETINMKhfdsfkcADIYALGL 275
Cdd:COG0515   127 GIVHRDIKPANILLTPDGRVKLIDFGIARALGGATLT---QTGTVVGTPGYMAPEqARGEPVDPR-------SDVYSLGV 196

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2318795510 276 VYWEIArrcnSGgvheeyQLPYydlvPSDPSIEEMRKVVCDQ-----KLRPNIPNWWQsyealRVMGKMM------Recw 344
Cdd:COG0515   197 TLYELL----TG------RPPF----DGDSPAELLRAHLREPppppsELRPDLPPALD-----AIVLRALakdpeeR--- 254

                         170
                  ....*....|..
gi 2318795510 345 YANGAARLTALR 356
Cdd:COG0515   255 YQSAAELAAALR 266

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP kinases serve as essential sensors of cellular stress. They are involved in regulating NF-kappaB and MAPK signaling, and are implicated in mediating cellular processes such as apoptosis, necroptosis, differentiation, and survival. RIP kinases contain a homologous N-terminal kinase domain and varying C-terminal domains. Higher vertebrates contain multiple RIP kinases, with mammals harboring at least five members. RIP1 and RIP2 harbor C-terminal domains from the Death domain (DD) superfamily while RIP4 contains ankyrin (ANK) repeats. RIP3 contain a RIP homotypic interaction motif (RHIM) that facilitates binding to RIP1. RIP1 and RIP3 are important in apoptosis and necroptosis, while RIP2 and RIP4 play roles in keratinocyte differentiation and inflammatory immune responses. The RIP subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2318795510 196 PGIAHRDLKSKNILVKKNGMCAIADLGLA-VRHDAVTDTIDIAPNQRVGTKRYMAPEVLDETI---NMKHfdsfkcaDIY 271
Cdd:cd13978   114 PPLLHHDLKPENILLDNHFHVKISDFGLSkLGMKSISANRRRGTENLGGTPIYMAPEAFDDFNkkpTSKS-------DVY 186

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2318795510 272 ALGLVYWEIARRcnsggvheeyQLPYYDlvpSDPSIEEMRKVVCDQklRPNIPNW--WQSYEALRVMGKMMRECWYANGA 349
Cdd:cd13978   187 SFAIVIWAVLTR----------KEPFEN---AINPLLIMQIVSKGD--RPSLDDIgrLKQIENVQELISLMIRCWDGNPD 251

                  ....*.
gi 2318795510 350 ARLTAL 355
Cdd:cd13978   252 ARPTFL 257

Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity kinase Myt1, the protein tyrosine kinase Wee1, and similar proteins. These proteins are cell cycle checkpoint kinases that are involved in the regulation of cyclin-dependent kinase CDK1, the master engine for mitosis. CDK1 is kept inactivated through phosphorylation of N-terminal thr (T14 by Myt1) and tyr (Y15 by Myt1 and Wee1) residues. Mitosis progression is ensured through activation of CDK1 by dephoshorylation and inactivation of Myt1/Wee1. The Wee1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2318795510 197 GIAHRDLKSKNILVKKNGMCAIADLGLAVRhdavtdtIDIAPNQRVGTKRYMAPEVLDEtiNMKHFDSfkcADIYALGLV 276
Cdd:cd13997   123 GIVHLDIKPDNIFISNKGTCKIGDFGLATR-------LETSGDVEEGDSRYLAPELLNE--NYTHLPK---ADIFSLGVT 190

                  ....*
gi 2318795510 277 YWEIA 281
Cdd:cd13997   191 VYEAA 195

Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class of kinases can not be predicted. Possible dual-specificity Ser/Thr/Tyr kinase.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2318795510  200 HRDLKSKNILVKKNGMCAIADLGLAVrhdAVTDTIDIAPNQRVGTKRYMAPEVLDEtinmKHFdSFKCaDIYALGLVYWE 279
Cdd:smart00221 126 HRDLAARNCLVGENLVVKISDFGLSR---DLYDDDYYKVKGGKLPIRWMAPESLKE----GKF-TSKS-DVWSFGVLLWE 196

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2318795510  280 IArrcnSGGvheeyQLPYYDLVPsdpsiEEMRKVVcDQKLRPNIPNwwqsyEALRVMGKMMRECWYANGAARLTALRIKK 359
Cdd:smart00221 197 IF----TLG-----EEPYPGMSN-----AEVLEYL-KKGYRLPKPP-----NCPPELYKLMLQCWAEDPEDRPTFSELVE 256

                   ..
gi 2318795510  360 TL 361
Cdd:smart00221 257 IL 258

Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include Schizosaccharomyces pombe Cdc7, Saccharomyces cerevisiae Cdc15, Arabidopsis thaliana mitogen-activated protein kinase kinase kinase (MAPKKK) epsilon, and related proteins. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Cdc7 is essential for cell division by playing a key role in the initiation of septum formation and cytokinesis. Budding yeast Cdc15 functions to coordinate mitotic exit with cytokinesis. Arabidopsis MAPKKK epsilon is required for pollen development in the plasma membrane. The Cdc7-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2318795510 197 GIAHRDLKSKNILVKKNGMCAIADLGLAVRHDAVTDTidiaPNQRVGTKRYMAPEVldetINMKHFdSFKCaDIYALGLV 276
Cdd:cd06627   119 GVIHRDIKGANILTTKDGLVKLADFGVATKLNEVEKD----ENSVVGTPYWMAPEV----IEMSGV-TTAS-DIWSVGCT 188

                          90       100
                  ....*....|....*....|....*.
gi 2318795510 277 YWEIArrcnsggvheEYQLPYYDLVP 302
Cdd:cd06627   189 VIELL----------TGNPPYYDLQP 204

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK4 is a MAPK kinase kinase that phosphorylates and activates the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. MEKK4 also plays roles in the re-polarization of the actin cytoskeleton in response to osmotic stress, in the proper closure of the neural tube, in cardiovascular development, and in immune responses. The MEKK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2318795510 197 GIAHRDLKSKNILVKKNGMCAIADLGLAVRHDAVTDTIDIAPNQR-VGTKRYMAPEVLDETINMKHFDSfkcADIYALGL 275
Cdd:cd06626   119 GIVHRDIKPANIFLDSNGLIKLGDFGSAVKLKNNTTTMAPGEVNSlVGTPAYMAPEVITGNKGEGHGRA---ADIWSLGC 195

                  ....*.
gi 2318795510 276 VYWEIA 281
Cdd:cd06626   196 VVLEMA 201

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. PAK deregulation is associated with tumor development. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). Group II PAKs contain a PBD and a catalytic domain, but lack other motifs found in group I PAKs. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. Group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX; no such binding has been demonstrated for group II PAKs. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2318795510 197 GIAHRDLKSKNILVKKNGMCAIADLGLAVRhdavtdtIDIAPNQR---VGTKRYMAPEVldetINMKHFDsFKCaDIYAL 273
Cdd:cd06614   117 NVIHRDIKSDNILLSKDGSVKLADFGFAAQ-------LTKEKSKRnsvVGTPYWMAPEV----IKRKDYG-PKV-DIWSL 183

                          90       100
                  ....*....|....*....|....*....
gi 2318795510 274 GLVYWEIArrcnsggvheEYQLPYYDLVP 302
Cdd:cd06614   184 GIMCIEMA----------EGEPPYLEEPP 202

Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein Kinase Kinase Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include the MAPKKKs Saccharomyces cerevisiae Bck1 and Schizosaccharomyces pombe Mkh1, and related proteins. Budding yeast Bck1 is part of the cell integrity MAPK pathway, which is activated by stresses and aggressions to the cell wall. The MAPKKK Bck1, MAPKKs Mkk1 and Mkk2, and the MAPK Slt2 make up the cascade that is important in the maintenance of cell wall homeostasis. Fission yeast Mkh1 is involved in MAPK cascades regulating cell morphology, cell wall integrity, salt resistance, and filamentous growth in response to stress. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The Bck1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2318795510 195 KPGIAHRDLKSKNILVKKNGMCAIADLGLAVRHDAVTDTiDIAPNQRvGTKRYMAPEVLDetiNMKHFDSFKCaDIYALG 274
Cdd:cd06629   126 SKGILHRDLKADNILVDLEGICKISDFGISKKSDDIYGN-NGATSMQ-GSVFWMAPEVIH---SQGQGYSAKV-DIWSLG 199